Facilitation of Corticostriatal Plasticity by the Amygdala Requires Ca²⁺-Induced Ca²⁺Release in the Ventral Striatum

Abstract

Motor learning and habit formation are thought to depend on corticostriatal synaptic plasticity. Moreover, basolateral amygdala (BLA) activity facilitates consolidation of striatal-dependent memories. Accordingly, BLA stimulation in vitro facilitates long-term potentiation (LTP) induction at corticostriatal synapses onto medium spiny neurons (MSNs). Although these effects were found to depend on N-methyl-d-aspartate (NMDA) receptor activation at BLA synapses and consequent Ca(2+) influx, it is unclear how this event can facilitate LTP at cortical synapses, even when the two inputs are not coactivated. Here, we aimed to shed light on this question, using whole cell recordings of MSNs in vitro. We first tested whether BLA inputs end at more proximal dendritic sites than cortical inputs. In this scenario, BLA synapses would experience stronger spike-related depolarizations and be in a strategic position to control the spread of second messengers. However, comparison of compound excitatory postsynaptic potentials and single-axon excitatory postsynaptic currents revealed that BLA and cortical synapses are intermingled. Next, we examined the sensitivity of cortical and BLA NMDA responses to ifenprodil because NR2A-containing NMDA receptors have faster kinetics than those containing NR2B subunits. However, the two inputs did not differ in this respect. Last, reasoning that propagating waves of Ca(2+)-induced Ca(2+) release (CICR) could bridge temporal gaps between the two inputs, we tested the effects of CICR inhibitors on the BLA facilitation of corticostriatal LTP induction. Pharmacological interference with CICR blocked corticostriatal LTP induction. Thus our results are consistent with the notion that NMDA-dependent Ca(2+) influx at BLA synapses initiates propagating waves of CICR, thereby biasing active corticostriatal inputs toward synaptic potentiation.

Interleukin-6 reduces NMDAR-mediated cytosolic Ca2+ overload and neuronal death via JAK/CaN signaling

“…On the other hand, Ca 2+ release from intracellular Ca 2+ stores depends on a high cytosolic Ca 2+ induced by extracellular Ca 2+ influx [41,42]. As shown in this study, NMDAR antagonist MK-801 completely blocked NMDA-evoked cytosolic Ca 2+ overload, confirming the important role of NMDAR channels in mediating cytosolic Ca 2+ overload.…”

New rules governing synaptic plasticity in core nucleus accumbens medium spiny neurons

“…Inputs from the thalamus readily undergo typical STDP, whereas cortical afferent synapses do not (Huang & Kandel, ; Humeau et al ., , ). Also, in a recent study in guinea pig, pairing APs with EPSPs evoked simultaneously from the cortex and amygdala in conditions close to ours (no GABA antagonist, EPSPs measured at RMP, and pairing frequency of 2 Hz) led to tLTP but not tLTD (Popescu et al ., ). Alternatively, dopamine receptors may influence the direction of long‐term plasticity as hinted by a recent work in the striatum (Shen et al ., ).…”

Interleukin-6 prevents NMDA-induced neuronal Ca2+overload via suppression of IP3 receptors

“…NMDA-triggered intracellular Ca 2þ overload involves several mechanisms, including Ca 2þ influx across neuronal membrane via NMDA-gated receptor channels and Ca 2þ release from intracellular Ca 2þ stores via Ca 2þ receptors, IP3R and RyR, located on the endoplasmic reticulum [28][29][30][31]. The Ca 2þ release from intracellular Ca 2þ stores is induced by high cytosolic Ca 2þ as a result of extracellular Ca 2þ influx and, therefore, it is termed Ca 2þ -induced Ca 2þ release [32,33]. In the present study, following incubation of neurons with MK-801, an NMDAR antagonist, NMDA did not induce a measurable increase in intracellular Ca 2þ levels in either the absence or the presence of IL-6.…”